ABSTRACT
OBJECTIVE: To clarify the expression and underlying network of long non-coding RNA (lncRNA) MCM3AP-AS1 in osteoarthritis (OA). METHODS: Human articular cartilage samples, OA model rats and IL-1ß-treated C28/I2 cells were used in this study. The expression changes of genes and proteins were assessed by real-time quantitative PCR (qRT-PCR) and western blot. Cell viability, apoptosis, autophagy and extracellular matrix (ECM) degradation were assessed by Cell Counting Kit-8 (CCK-8), immunohistochemistry (IHC), flow cytometry, immunofluorescence and western blot assays, respectively. Molecule interactions were validated by dual luciferase and Chromatin immunoprecipitation (ChIP) assays. H&E staining was used to detect the pathological changes of cartilage. RESULTS: MCM3AP-AS1 was upregulated in OA patients and IL-1ß-induced chondrocytes. Knockdown of MCM3AP-AS1 enhanced autophagy, while alleviated ECM degradation and cartilage injury. Mechanistically, overexpression of SOX4 boosted the transcription of MCM3AP-AS1. Moreover, MCM3AP-AS1 functioned as a molecular sponge or epigenetic regulator of miR-149-5p to facilitate Notch1 expression. Functional rescue experiments showed that either inhibition of miR-149-5p nor ectopic expression of Notch1 dramatically weakened the biological impacts of MCM3AP-AS1 silencing. CONCLUSION: These finding demonstrated that SOX4-activated MCM3AP-AS1 aggravated OA progression by modulating autophagy and ECM degradation via targeting miR-149-5p/Notch1 axis. These data supported that inhibition of MCM3AP-AS1 might be a potential treatment strategy of OA.
Subject(s)
MicroRNAs , Osteoarthritis , RNA, Long Noncoding , Acetyltransferases/genetics , Acetyltransferases/metabolism , Animals , Apoptosis/physiology , Cell Proliferation , Chondrocytes/metabolism , Humans , Intracellular Signaling Peptides and Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Osteoarthritis/genetics , Osteoarthritis/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Rats , Receptor, Notch1/genetics , Receptor, Notch1/metabolism , SOXC Transcription Factors/metabolism , Signal TransductionABSTRACT
OBJECTIVE: To improve the diagnosis, therapy and prognosis of testicular tumor in Mongolian men. METHODS: A retrospective review of 35 cases of testicular tumors in Mongolian men from seven medical centers dated from 1990 to 2004 was performed. RESULTS: The usual presentation of a testicular tumor was a nodular or painless swelling of one gonad. The mean delay in diagnosis was 40.03 +/- 53.45 weeks. For 16 patients, delay in diagnosis was more than or equal to six months. The histologic composition of this series was 21 (60%) seminoma, 10 (28.6%) nonseminoma, 2 (5.7%) lymphoma, 1 (2.35%) fibroneuroma and 1 (2.35%) leiomyoma. Regarding stage, 22, 2, and 5 of 29 germ cell tumors were seen initially as stage I, II, and III, respectively. Combined therapy, including radical orchiectomy, radiotherapy and chemotherapy, were taken. 29 cases have been followed for 2 months to 10 years, 4 out of them died of distant metastasis, one died of other disease, one lives with tumor, the others live without relapse and metastasis. Three and 5-year survival rates for Mongolian patients with seminoma and nonseminoma were 95.0%, 95.0%, 57.1% and 42.8%, respectively. CONCLUSION: In this article, the rate of seminoma to germ cell tumors is higher than that of general population. There is an increased mean delay in diagnosis for Mongolian patients. Three and 5-year survival rates for nonseminoma are lower than that for seminoma. Better public awareness regarding testicular tumor in this population, advances in diagnosis and therapy will help to improve therapeutic effectiveness and prognosis.